crossing96/oncoscreening huggingface dataset:
Current status of management and outcomes of muscle-invasive bladder cancer in Yemen: a retrospective observational study.	BACKGROUND: The lack of a cohesive diagnostic and therapeutic framework for muscle-invasive bladder cancer (MIBC) in Yemen has resulted in significant variability in patient care. This study evaluates oncological outcomes and survival rates after radical cystectomy (RC) for MIBC patients in Yemen. METHODS: We conducted a retrospective analysis of 300 MIBC patients who underwent RC between 2006 and 2020. Demographics, histopathological findings, and survival data were meticulously collected. Kaplan-Meier survival analysis estimated survival probabilities, while prognostic factors were evaluated using the log-rank test. RESULTS: The median patient age was 67 years (IQR 65-70), with a male predominance (n=184, 61.3%). Ileal loop reconstruction was the primary method of urinary diversion (n=234, 78.0%). Urothelial carcinoma was the predominant diagnosis (n=246, 82.0%), followed by squamous cell carcinoma (n=42, 14.0%). Postoperative complications occurred in 93 patients (31.0%), primarily Grade I (n=61, 20.3%). Overall survival was 71.7% (n 215), with 28.3% mortality due to non-cancer-related (n=43, 14.3%) and bladder cancer-related causes (n=35, 11.7%). The median overall survival was 191 months, with 1-year, 3-year, 5-year, and 10-year survival rates of 99%, 93%, 88%, and 82%, respectively. In the multivariate analysis, non-ileal conduit diversion (Hazard Ratio [HR] 5.21, 95% Confidence Interval [CI]: 1.80-15.00, p=0.003), Stage IV disease (HR 2.76, 95% CI: 1.01-7.61, p=0.050), lymph node positivity (HR 2.92, 95% CI: 1.15-7.42, p=0.022), and squamous cell carcinoma (HR 3.09, 95% CI: 1.25-7.63, p=0.022) were identified as predictors of mortality. CONCLUSIONS: This study highlights the urgent need for improved bladder cancer care in Yemen. Late-stage diagnosis and suboptimal surgical methods critically affect survival. Addressing these issues requires prioritizing early detection and standardized surgical techniques to develop effective care pathways for MIBC patients.	bladder
The Value of Circulating Tumor DNA in the Prognostic Diagnosis of Bladder Cancer: A Systematic Review and Meta-Analysis.	INTRODUCTION: Circulating tumor DNA (ctDNA) is a noninvasive liquid biopsy technique that can reflect the dynamic changes of tumors in real time. This study aims to clarify the predictive value of ctDNA detection for disease progression and metastasis risk in bladder cancer patients through systematic review and meta-analysis, providing a scientific basis for clinicians' individualized treatment decisions and risk stratification management for patients. METHODS: Studies related to ctDNA in prognostic assessment of bladder cancer were screened by systematically searching PubMed, Cochrane Library, Web of Science, Willey library, CNKI, and other databases, and the search was from inception to December 2024, and the data were extracted and analyzed by Meta-analysis. RESULTS: A total of 9 papers were included, and the results showed that ctDNA testing had a sensitivity of 0.68 (95% CI: 0.54-0.78), specificity of 0.76 (95% CI: 0.51-0.90), and an area under the curve of 0.75 (95% CI: 0.71-0.79), suggesting that it has a moderate level of diagnostic efficacy in the assessment of prognosis in bladder cancer. Positive likelihood ratio and negative likelihood ratio were 2.8 (95% CI: 1.24-6.35) and 0.43 (95% CI: 0.28-0.65), respectively, with a diagnostic odds ratio of 6.56 (95% CI: 2.12-20.33). Fagan's nomogram analysis showed that when the prior probability was 50%, the posttest probability increased to 74% for positive results and decreased to 30% for negative results. Deeks' funnel plot analysis indicated no significant publication bias (p = 0.24). A high level of heterogeneity (I2 > 80%) was observed among the studies, which may stem from differences in detection techniques, disease stages of patients, and follow-up periods. Publication bias analysis revealed no significant bias (p = 0.24). CONCLUSION: ctDNA demonstrates some clinical application value in the prognostic assessment of bladder cancer and can assist in predicting patient recurrence and survival. However, its independent predictive efficacy is not enough to replace traditional assessment methods. Future studies should aim to optimize the detection technology, unify the study design, expand the sample size, and combine multi-omics data for joint analysis, in order to further improve its potential application in the prognostic assessment of bladder cancer.	bladder
The nephroprotective effect of metformin with cisplatin in bladder cancer: randomized clinical trial.	PURPOSE: Cisplatin-based combination chemotherapy is the mainstay treatment strategy in various forms of carcinomas and sarcomas. However, its dosage and therapeutic efficacy are significantly limited by its nephrotoxicity. Based on metformin renal benefits in different studies, the study aims to determine safety and the potential nephroprotective effect of metformin when used with cisplatin in patients with bladder cancer. METHODS: This was a prospective, randomized, parallel, controlled, open-label study in which 78 chemotherapy naïve bladder cancer patients aged 18-65 years and would receive gemcitabine/cisplatin regimen were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving cisplatin standard-of-care regimen, whereas metformin (500 mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for four cycles of gemcitabine/cisplatin with assessment of renal function tests, serum neutrophil gelatinase-associated lipocalin (NGAL), cystatin-c, and metformin's adverse effects. RESULTS: Serum creatinine, serum NGAL, and cystatin-C significantly increased in the control group only (P < 0.001). Estimated glomerular filtration rate (eGFR) significantly declines in the control group only (P < 0.001). On the contrary, serum NGAL significantly improved in the treatment group (P = 0.02) with stable and normal mean value of serum creatinine, eGFR, and cystatin-C without a concomitant significant increase in adverse events, such as hypoglycemia, gastrointestinal symptoms, or weight loss compared to the control group. CONCLUSION: Metformin prevented renal damage and deterioration in kidney function in cisplatin-treated patients. Therefore, it is a promising agent in reducing cisplatin-induced nephrotoxicity. The study was registered in ClinicalTrials.gov on December, 16, 2023, Identifier Number NCT06215976.	bladder
Impact of marriage on diagnosis and survival in patients with urological cancers.	The protective role of marriage has been identified in various cancers, but its effect on the overall urological system remains unclear. Patients diagnosed with bladder cancer (BCa), renal cell carcinoma (RCC), and upper tract urothelial carcinoma (UTUC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into married and unmarried groups based on their marital status. A binary multivariable logistic regression was used to explore the effect of marriage on the diagnosis of urological cancers. One-to-one propensity score matching (PSM) was employed to reduce baseline differences between the two groups. Multivariable Cox regression analysis and subgroup analysis were conducted to investigate the impact of marriage on cancer-specific survival (CSS). A total of 162,544 patients were included in the study, with a median follow-up period of 6.2 years (IQR 2.3-9.8 years). Among them, 104,706 (64.4%) were married, and 57,838 (35.6%) were unmarried. Married patients had a lower risk of being diagnosed with stage III/IV disease compared to unmarried patients (OR 0.94, 95% CI 0.92-0.96, p < 0.001), but this trend was only significant in BCa (OR 0.88, 95% CI 0.84-0.91, p < 0.001), but not in RCC (OR 0.98, 95% CI 0.94-1.01, p = 0.172) or UTUC (OR 1.03, 95% CI 0.95-1.12, p = 0.523). After PSM, 47,975 patients were included in each group, and marriage was found to be an independent protective prognostic factor for CSS (HR 0.81, 95% CI 0.79-0.83, p < 0.001), but this was not significant in UTUC (HR 0.95, 95% CI 0.88-1.03, p = 0.244). Across the entire urological system, marriage is an independent protective predictor for both diagnosis and survival, but the effect varies among different types of cancers.	bladder
Low T cell diversity associates with poor outcome in bladder cancer: A comprehensive longitudinal analysis of the T cell receptor repertoire.	T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. Here, we investigate the clinical relevance of the T cell receptor (TCR) repertoire in patients with bladder cancer. In advanced-stage disease, low pre-treatment peripheral TCR diversity is associated with worse overall survival (p = 0.024), particularly when coupled with low circulating T cell fractions (p = 0.00049). These low-diversity repertoires are dominated by hyper-expanded clones that persist throughout treatment. Further longitudinal analysis reveals reductions in TCR diversity after treatment, indicating adverse effects on the immune system. In early-stage disease, immunotherapy increases TCR diversity in patients with good outcomes. Furthermore, single-cell sequencing identifies most hyper-expanded clones as cytotoxic T cells, while non-expanded clones are predominantly naive T cells. Overall, this highlights TCR diversity as a promising biomarker, offering opportunities for tailored oncological treatments to enhance clinical outcomes.	bladder
DNMT1 promotes bladder cancer progression and immune escape by inhibiting MYH11 expression by methylating its promoter.	BACKGROUND: Bladder cancer (BC) is a fatal malignancy of the urinary tract with limited effective biomarkers and therapeutic targets. This paper delved into the mechanism of MYH11 and DNMT1 in BC progression. METHODS: Differential genes obtained from the GSE3167 dataset were analyzed by the R language limma package. RT-qPCR, Western blot, and immunohistochemistry were carried out to assess MYH11 and DNMT1 expression in BC cell lines and BC tissues. Cell migration, invasion, proliferation, and apoptosis were detected by Transwell assay, CCK-8, and TUNEL after different lentiviral vector treatments. MB49 cells with different infections were administered into mice to monitor tumor growth and immune escape. Flow cytometry detected the rate of CD45(+)CD4(+)-positive cells in the tumor tissues and PD-1 and TIM-3 expression in CD4(+) T cells. MYH11 methylation was analyzed using the qMSP assay. ChIP and dual-luciferase assay were used for regulatory assays. RESULTS: MYH11 was lowly expressed in BC. Overexpression of MYH11 inhibited the malignant progression of BC cells, promoted anti-tumor immune responses of CD4(+) T cells, and inhibited immune escape and tumor development in mice. DNMT1 inhibited MYH11 expression by elevating MYH11 promoter methylation. DNMT1 inhibition impeded the immune escape of BC cells, which was reversed by silencing MYH11. DNMT1 silencing prevented immune escape via transcriptional activation of MYH11 and hindered tumor growth in mice. CONCLUSION: DNMT1 promotes immune escape and malignant progression of BC by methylating the promoter of MYH11.	bladder
Optimizing extraction of microbial DNA from urine: Advancing urinary microbiome research in bladder cancer.	PURPOSE: This study aimed to evaluate and optimize microbial DNA extraction methods from urine, a non-invasive sample source, to enhance DNA quality, purity, and reliability for urinary microbiome research and biomarker discovery in bladder cancer. MATERIALS AND METHODS: A total of 302 individuals (258 with genitourinary cancers and 44 with benign urologic diseases) participated in this study. Urine samples were collected via sterile catheterization, resulting in 445 vials for microbial analysis. DNA extraction was performed using three protocols: the standard protocol (SP), water dilution protocol (WDP), and chelation-assisted protocol (CAP). DNA quality (concentration, purity, and contamination levels) was assessed using NanoDrop spectrophotometry. Microbial analysis was conducted on 138 samples (108 cancerous and 30 benign) using 16S rRNA sequencing. Prior to sequencing on the Illumina MiSeq platform, Victor 3 fluorometry was used for validation. RESULTS: WDP outperformed other methods, achieving significantly higher 260/280 and 260/230 ratios, indicating superior DNA purity and reduced contamination, while maintaining reliable DNA yields. CAP was excluded due to poor performance across all metrics. Microbial abundance was significantly higher in WDP-extracted samples (p<0.0001), whereas SP demonstrated higher alpha diversity indices (p<0.01), likely due to improved detection of low-abundance taxa. Beta diversity analysis showed no significant compositional differences between SP and WDP (p=1.0), supporting the reliability of WDP for microbiome research. CONCLUSIONS: WDP is a highly effective and reliable method for microbial DNA extraction from urine, ensuring high-quality and reproducible results. Future research should address sample variability and crystal precipitation to further refine microbiome-based diagnostics and therapeutics.	bladder
ɑ1,3-mannosyltransferase promotes the malignant progression of bladder cancer through activating TNF signaling pathway.	BACKGROUND: Bladder cancer (BCa) is the most prevalent malignancy of the urinary system. Aberrant glycosylation, driven by specific glycosyltransferases (GTs), plays a pivotal role in various carcinogenic processes. However, the role of GTs-related glycobiomarkers and their underlying mechanisms in BCa remain poorly understood. METHODS: A diagnostic model based on GTs was constructed and validated using multiple bioinformatics tools. The diagnostic and prognostic value, biological functions and potential targeted drugs were assessed using R packages, K-M plotter and molecular docking. The functional impact and mechanism of ALG3 in BCa were investigated through functional assays, RNA sequencing, immunoprecipitation, and lectin pull down assays. RESULTS: A diagnostic model comprising six GTs (ALG3, POMT2, UGCG, XXYLT1, COLGALT1, and A4GALT) was established, demonstrating high diagnostic accuracy for BCa (AUC: 0.966; sensitivity: 88.5%; specificity: 92.6%), which was further validated. Among these, ALG3 and POMT2 belong to the mannosyltransferase family, with ALG3 identified as a more reliable diagnostic glycobiomarker than POMT2 for BCa detection. GSVA analysis revealed that ALG3 was significantly enriched in Umbrella cells, suggesting its potential role in influencing BCa cell fate. Overexpression of ALG3 promoted cell proliferation and metastasis by modulating CD44 N-glycosylation and activating the TNF signaling pathway, confirming its role as a tumor promoter and oncogene in BCa progression. Moreover, ALG3 was identified as a novel target of miR-142-5p. Four potential small molecule inhibitors of ALG3 were identified, with selumetinib emerging as a promising candidate. CONCLUSIONS: ALG3 contributed to BCa progression via CD44 N-glycosylation and TNF pathway, positioning it as a promising serum glycobiomarker, a feasible therapeutic target, and a valuable reference for personalized and precision medicine in BCa.	bladder
Cabozantinib plus Pembrolizumab as First-line Therapy for Cisplatin-ineligible Advanced Urothelial Carcinoma: The PemCab Trial.	BACKGROUND AND OBJECTIVE: Pembrolizumab monotherapy is approved for patients with platinum-ineligible metastatic urothelial carcinoma (mUC). Cabozantinib is a multireceptor tyrosine kinase inhibitor with activity against MET and VEGFR2 and is approved as monotherapy or in combination with a PD-1 inhibitor for other malignancies. The objective was to determine the safety and efficacy of pembrolizumab + cabozantinib as first-line treatment for patients with mUC. METHODS: In this open-label, single-arm, multicenter, phase 2 study, patients received pembrolizumab 200 mg every 3 wk + cabozantinib 40 mg daily. Key inclusion criteria were locally advanced UC or mUC, Eastern Cooperative Oncology Group performance status 0-2, ineligible for or refused cisplatin, and no prior PD-1/L1 inhibitor. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). According to the statistical plan, in a cohort of 35 evaluable participants, the lower bound of the 95% confidence interval (CI) would extend no more than 26% from the ORR observed, and in a scenario with ≥17 objective responses, the CI would exclude 32%. KEY FINDINGS AND LIMITATIONS: Responses were observed in 16 of 35 evaluable patients, with an ORR of 46% (95% CI 31-62%). Median PFS and OS were 8 mo (95% CI 5-13) and 17 mo (95% CI 13-not reached), respectively. The most common treatment-emergent adverse events (any grade) were diarrhea (58%), fatigue (56%), pruritus (39%), nausea (36%), palmar-plantar erythrodysesthesia (36%), and a decrease in appetite (33%). CONCLUSIONS AND CLINICAL IMPLICATIONS: This phase 2 trial of pembrolizumab + cabozantinib demonstrated a manageable toxicity profile and promising efficacy as a first-line therapy combination for cisplatin-ineligible patients with mUC.	bladder
Comparable Diagnostic Performance of 99m Tc-FAPI Scintigraphy and Contrast-enhanced CT in Restaging a Rare Case of Metastatic Colon Adenocarcinoma to the Urachus.	We present a case of a 33-year-old man with gross hematuria and dysuria, leading to the discovery of a bladder and urachal mass. Imaging revealed significant bladder wall thickening and regional lymph node metastases. Following transurethral resection, histopathologic and immunohistochemical analyses were consistent with the urachal metastatic adenocarcinoma with colon origin. After chemotherapy, a 99m Tc-FAPI-46 scintigraphy was performed, revealing favorable FAPI uptake in all tumoral lesions detected in the contrast-enhanced CT scan. This case highlights the diagnostic utility of FAPI-46, as a novel radiotracer, in evaluating urachal neoplasms and its potential for theranostic approaches.	bladder
Unleashing the therapeutic potential of tumor-draining lymph nodes: spotlight on bladder cancer.	Tumor-draining lymph nodes (TDLNs) are often involved during the metastasis of bladder cancer (BC), which is associated with a poor prognosis. Recent studies have shown that TDLNs are a major source of host anti-tumor immunity, which can impede tumor progression and favor tumor immunotherapy. However, during tumor progression, various tumor-derived mediators modulate the TDLN microenvironment, impairing their protective function. Ultimately, TDLNs provide the soil for the proliferation and dissemination of tumor cells. Therefore, surgical removal of TDLNs is commonly recommended in various solid tumors to prevent metastasis, but this poses significant challenges for leveraging TDLNs in immunotherapy. Additionally, lymph node dissection (LND) has not shown survival benefits in some tumors. Hence, the decision to remove TDLNs in oncological treatment needs to be reconsidered. Herein, we spotlight the TDLNs of BC and introduce how BC cells modulate stromal cells and immune cells to shape an immunosuppressive TDLN microenvironment for BC progression. We summarize the existing therapeutic strategies to reinvigorate anti-tumor immunity in TDLNs. Furthermore, we discuss whether to preserve TDLNs and the role of LND during oncological treatment.	bladder
Clinical Outcomes, Genomic Heterogeneity, and Therapeutic Considerations Across Histologic Subtypes of Urothelial Carcinoma.	BACKGROUND AND OBJECTIVE: Divergent differentiation and histologic subtypes are common findings in urothelial carcinoma (UC). Clinically relevant genomic alterations and oncogenic drivers of individual subtypes remain poorly defined. We characterized surgical outcomes and the genomic landscape of UC with aberrant histology (UCAH), with a focus on biomarkers and targetable alterations. METHODS: The clinical cohort comprised 3052 patients who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy. Targeted exon sequencing was performed for a genomic cohort of 1060 bladder tumors from RC or transurethral resection specimens. We characterized the frequency of oncogenic mutations and targetable alterations, and the tumor mutational burden (TMB) of each subtype. We defined the clonal relatedness of morphologically distinct regions of tumors with mixed histology. KEY FINDINGS AND LIMITATIONS: Patients with plasmacytoid, micropapillary, sarcomatoid, or mixed-histology tumors had worse cancer-specific survival than patients with pure urothelial histology. ERBB2, FGFR3, and PTEN alterations were most frequent in micropapillary, nested/squamous, and sarcomatoid UC, respectively. TMB was highest in plasmacytoid, neuroendocrine, and micropapillary tumors. Regions of mixed histology had shared clonal origins, but exceptions were observed. The retrospective design and potential for selection bias are limitations of our study. CONCLUSIONS AND CLINICAL IMPLICATIONS: UCAH tumors have distinct patterns of genomic alterations, which may be targetable via novel therapies and have implications for clinical trial inclusion. Biomarker-driven systemic therapy should be explored in patients with histologic subtypes that are associated with worse clinical outcomes.	bladder
Presence of an Artificial Intelligence-powered Predictive Biomarker Is Associated with a Poor Response to Intravesical Bacillus Calmette-Guerin but Not to Intravesical Sequential Gemcitabine/Docetaxel in Patients with High-grade Non-muscle-invasive Bladder Cancer.	Intravesical bacillus Calmette-Guerin (BCG) is considered first-line adjuvant therapy for high-risk or high-grade non-muscle-invasive bladder cancer (NMIBC). Recently, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has emerged as a promising alternative to intravesical BCG. Biomarkers to select the optimal treatment regimen could facilitate clinical decision-making. The Computational Histologic Artificial Intelligence (CHAI) platform was previously used to develop an artificial intelligence-augmented histologic assay (CHAI biomarker) that identified patients with NMIBC at an increased risk of recurrence and progression events following BCG treatment. In this study, we assessed use of the CHAI biomarker among patients with treatment-naive high-grade NMIBC who received intravesical BCG or Gem/Doce. Among patients with the presence of the CHAI biomarker, those treated with BCG had a 24-mo high-grade recurrence-free survival (HG-RFS) rate of 56% (95% confidence interval [CI] 43-73%) and those treated with Gem/Doce had an HG-RFS rate of 90% (95% CI 79-100%; hazard ratio [HR] 5.4, 95% CI 1.6-18.3, p = 0.007). Among patients with an absence of the CHAI biomarker, those treated with BCG or Gem/Doce had no significant difference in HG-RFS (HR 1.3, 95% CI 0.6-2.6, p = 0.5). The interaction term between the CHAI biomarker and the treatment type was significant (p = 0.029), indicating an association between the biomarker and the clinical outcome that is dependent on the treatment received. This study suggests that the CHAI biomarker predicts which specific high-grade NMIBC patients are less likely to benefit from BCG and may benefit from alternative treatments including, potentially, Gem/Doce.	bladder